Bipolar comorbidity, neurobiology and clinical presentation
Introduction. Bipolar disorder presents us with a complex phenotype that can include virtually all the key phenomenological entities we recognise in psychiatry - depression, mania, psychosis, anxiety, substance misuse, cognitive impairment, neuroendocrine abnormality, sleep disturbance and distinctively variable illness course. The fact that these apparently independent dimensions cluster within the single diagnosis of bipolar disorder is a very challenging fact . Does it mean that the dimensions are themselves related to each other and severity in one will entail severity in the other - perhaps because of common developmental variations in biology or the cumulative effects of illness? Or are cases of bipolar disorder simply those people who sit on the wrong end of these multiple domains, all of which can behave relatively independently? Can diagnosis usefully continue to be categorical, without measuring the dimensions that characterise the disease? Methodology. Epidemiological surveys to establish clinical co-morbidity. To determine the neurobiology, we measured amygdala responses to subliminal presentation of fearful and happy facial expressions with functional magnetic resonance imaging (fMRI) and startle responses while viewing images differently valenced for emotional content in unmedicated, remitted patients with a history of bipolar and unipolar disorder. Results. Bipolar patients show high levels of co-morbidity for anxiety. Enhanced amygdala responses were seen in both patient groups relative to controls; however, this was specific to fearful facial expressions in the unipolar group, and happy facial expressions in the bipolar group. Baseline startle responsiveness is increased in bipolar subjects perhaps reflecting the vulnerability to anxiety disorder. Conclusions. Abnormal amygdala responses and startle response to emotional stimuli apparently persist following clinical remission and medication withdrawal in patients with mood disorder. Our results suggest some specificity in the abnormal amygdala responses in unipolar and bipolar patients consistent with the differing clinical presentations and treatment response of the two disorders. The neurobiology offers the possibility of surrogate measures of drug responsiveness and response to treatment  . © 2007 Taylor & Francis.